Chapter 4-Webster The Origin of Biopotentials

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Chapter 4-WebsterThe Origin of Biopotentials
Note Some of the figures in this presentation
have been taken from reliable websites in the
internet and textbooks.
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Bioelectric Signals

• Bioelectrical potential is a result of
  electrochemical activity across the membrane of
  the cell.
• Bioelectrical signals are generated by excitable
  cells such as nervous, muscular, and glandular
  cells.
• The resting potential of the cell is -40 to -90
  mV relative to the outside and 60 mV during
  action potential.
• Volume conductor electric field is an electric
  field generated by many excitable cells of the
  specific organ such as the heart.
• Typical types of bioelectric signals
• Electrocardiogram (ECG, EKG)
• Electroencephalogram (EEG)
• Electromyogram (EMG)
• Electroretinogram (ERG)

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Bioelectric Signals
L latent period transmission time from stimulus
to recording site.
Potential inside cells -40 to -90 mV relative to
the outside. Cell membrane is lipoprotein
complex that is impermeable to intracellular
protein and other organic anions (A-)
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The Resting State

• Membrane at resting state is
• slightly permeable to Na and freely permeable to
  K and Cl-
• permeability of potassium PK is 50 to 100 times
  larger than the permeability to sodium ion PNa.

2.5 mmol/liter of K
2.5 mmol/liter of K
140 mmol/liter of K
140 mmol/liter of K
Cl-
K
Cl-
K
Electric Field
- - -


- - -
External media
External media
Internal media
Internal media
Frog skeletal muscle membrane
Frog skeletal muscle membrane
Diffusional force electrical force
Diffusional force gt electrical force
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Sodium-Potassium Pump
Keeping the cell at resting state requires active
transport of ionic species against their normal
electrochemical gradients. Sodium-potassium pump
is an active transport that transports Na out of
the cell and K into the cell in ration 3Na2K
Energy for the pump is provided by a cellular
energy adenosine triphosphate (ATP)
2.5 mmol/liter of K
140 mmol/liter of K
2K
3Na
- -


- -
Electric Field
External media
Internal media
Frog skeletal muscle membrane
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Equilibrium Potential- Nernst Equation
At 37 oC
Where n is the valence of K.
E Equilibrium transmembrane resting potential,
net current is zero PM permeability coefficient
of the membrane for ionic species M Mi and Mo
the intracellular and extracellular
concentrations of M in moles/ liter R Universal
gas constant (8.31 j/mol.k) T Absolute
temperature in K F Faraday constant (96500
c/equivalent)
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Example 4.1
For the frog skeletal muscle, typical values for
the intracellular and extracellular
concentrations for the major ion species (in
millimoles per liter) are as follows. Species In
tracellular Extracellular Na 12 145 K 155
4 Cl- 4 120 Assuming room temperature (20
oC) and typical values of permeability
coefficient for the frog skeletal muscle (PNa
210-8 cm/s, Pk 210-6 cm/s, and PCl 410-6
cm/s), calculate the equilibrium resting
potential for this membrane, using the Goldman
equation.
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The Active State
Membrane at resting state is polarized (more
negative inside the cell) Depolarization
lessening the magnitude of cell polarization by
making inside the cell less negative. Hyperpolari
zation increasing the magnitude of cell
polarization by making inside the cell more
negative. A stimulus that depolarize the cell to
a potential higher than the threshold potential
causes the cell to generate an action potential.
Action Potential - Rate 1000 action
potential per second for nerve - All-or-none
- ?v 120 mV for nerve
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Action Potential
If stimulus depolarize the cell such that Vcell gt
Vthreshold an action potential is generated.
External media
Internal media
2.5 mmol/liter of K
140 mmol/liter of K
Na
- -

Electric Field

-
K
- -

-
Electric Field

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Action Potential
Absolute refractory period membrane can not
respond to any stimulus. Relative refractory
period membrane can respond to intense stimulus.
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Action Potential
Action potential travel at one direction.
Myelination reduces leakage currents and improve
transmission rate by a factor of approximately 20.
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Diagram of network equivalent circuit of a small
length (Dz) of an unmyelinated nerve fiber or a
skeletal muscle fiber The membrane proper is
characterized by specific membrane capacitance Cm
(mF/cm2) and specific membrane conductances gNa,
gK, and gCl in mS/cm2 (millisiemens/cm2). Here an
average specific leakage conductance is included
that corresponds to ionic current from sources
other than Na and K (for example, Cl-). This
term is usually neglected. The cell cytoplasm is
considered simply resistive, as is the external
bathing medium these media may thus be
characterized by the resistance per unit length
ri and ro (?/cm), respectively. Here im is the
transmembrane current per unit length (A/cm), and
?i and ?o are the internal and external
potentials ? at point z, respectively.
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Volume Conductor Fields
Volume conductor fields is an electric field
generated by active cell (current source) or
cells immersed in a volume conductor medium of
resistivity ? such as the body fluids. Potential
Waveform at the outer surface of membrane for
monophasic action potential 1- triphasic in
nature 2- greater spatial extent than the action
potential 3- much smaller in peak to peak
magnitude 4- relatively constant in propagation
along the excited cell. - Potential in the
extracellular medium of a single fiber fall off
exponentially in magnitude with increasing radial
distance from the fiber (potential zero within
fifteen fiber radii) - Potential depends on
medium Properties.
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Volume Conductor Fields
The extracellular field of an active nerve trunk
with its thousands of component nerve fibers
simultaneously activated is similar to the field
of a single fiber.
Figure 4.5 Extracellular field potentials
(average of 128 responses) were recorded at the
surface of an active (1-mm-diameter) frog sciatic
nerve in an extensive volume conductor. The
potential was recorded with (a) both motor and
sensory components excited (Sm Ss), (b) only
motor nerve components excited (Sm), and (c) only
sensory nerve components excited (Ss).
Sensory branch
Motor branch
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Peripheral Nervous System

• Spinal nervous system is functionally organized
  on the basis of what is called the reflex arc
• A sense organ (ear-sound, eye-light,
  skin-temperature)
• A sensory nerve (transmit information to the
  CNS)
• The CNS serves as a central integrating station
• Motor nerve communication link between CNS and
  peripheral muscle
• Effector organ skeletal muscle fibers

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Example of reflex arc
Example of reflex arc
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(Feedback)
Schematic diagram of a muscle-length control
system for a peripheral muscle (biceps) (a)
Anatomical diagram of limb system, showing
interconnections. (b) Block diagram of control
system.
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Junctional Transmission
Synapses intercommunicating links between
neurons Neuromuscular junctions communicating
links between neurons and muscle fibers at
end-plate region.
Neuromuscular junction (20nm thickness) release
neurotransmitter substance Acetylcholine
(Ach) Time delay due to junction is 0.5 to 1
msec Excitation-contraction time delay due to
muscle contraction
Neuron
Muscle
end-plate region
At high stimulation rates, the mechanical
response fuse into one continuous contraction
called a tetanus (mechanical response summates).
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Neuromuscular junction
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Electroneurogram (ENG)

• Recording the field potential of an excited
  nerve.
• Neural field potential is generated by
• - Sensory component
• - Motor component
• Parameters for diagnosing peripheral nerve
  disorder
• Conduction velocity
• Latency
• Characteristic of field potentials evoked in
  muscle supplied by the stimulated nerve (temporal
  dispersion)
• Amplitude of field potentials of nerve fibers lt
  extracellular potentials from muscle fibers.

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Conduction Velocity of a Nerve
V(t)
S2
S1
R

-

-
Reference
Muscle
D
S2
V(t)
D
L2
t
Velocity
u

S1
L1- L2

V(t)
1 mV
L1
2 ms
Figure 4.7 Measurement of neural conduction
velocity via measurement of latency of evoked
electrical response in muscle. The nerve was
stimulated at two different sites a known
distance D apart.
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Field Potential of Sensory Nerves
Extracellular field response from the sensory
nerves of the median or ulnar nerves
To excite the large, rapidly conducting sensory
nerve fibers but not small pain fibers or
surrounding muscle, apply brief, intense stimulus
( square pulse with amplitude 100-V and duration
100-300 ?sec). To prevent artifact signal from
muscle movement position the limb in a
comfortable posture.
Figure 4.8 Sensory nerve action potentials evoked
from median nerve of a healthy subject at elbow
and wrist after stimulation of index finger with
ring electrodes. The potential at the wrist is
triphasic and of much larger magnitude than the
delayed potential recorded at the elbow.
Considering the median nerve to be of the same
size and shape at the elbow as at the wrist, we
find that the difference in magnitude and
waveshape of the potentials is due to the size of
the volume conductor at each location and the
radial distance of the measurement point from the
neural source.
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Reflexly Evoked Field Potentials
Some times when a peripheral nerve is stimulated,
a two evoked potentials are recorded in the
muscle the nerve supplies. The time difference
between the two potentials determined by the
distance between the stimulus and the muscle.
Stimulated nerve posterior tibial nerve Muscle
gastrocnemius
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Reflexly Evoked Field Potentials
Low intensity stimulus stimulate only the large
sensory fibers that conduct toward the CNS. No M
wave
Medium intensity stimulus stimulate smaller motor
fibers in addition to the large sensory fibers.
Motor fibers produce a direct muscle response the
M wave.
With strong stimuli, the excited motor fibers are
in their refractory period so only the M wave is
produced.
Figure 4.9 The H reflex The four traces show
potentials evoked by stimulation of the medial
popliteal nerve with pulses of increasing
magnitude (the stimulus artifact increases with
stimulus magnitude). The later potential or H
wave is a low-threshold response, maximally
evoked by a stimulus too weak to evoke the
muscular response (M wave). As the M wave
increases in magnitude, the H wave diminishes.
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Electromyogram (EMG)

• Skeletal muscle is organized functionally on the
  basis of the single motor unit (SMU).
• SMU is the smallest unit that can be activated by
  a volitional effort where all muscle fibers are
  activated synchronously.
• SMU may contain 10 to 2000 muscle fibers,
  depending on the location of the muscle.
• Factors for muscle varying strength
• Number of muscle fibers contracting within a
  muscle
• Tension developed by each contracting fiber

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Muscle Fiber (Cell)
http//www.blackwellpublishing.com/matthews/myosin
.html
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Figure 4.10 Diagram of a single motor unit
(SMU), which consists of a single motoneuron and
the group of skeletal muscle fibers that it
innervates. Length transducers muscle spindles,
Figure 4.6(a) in the muscle activate sensory
nerve fibers whose cell bodies are located in the
dorsal root ganglion. These bipolar neurons send
axonal projections to the spinal cord that divide
into a descending and an ascending branch. The
descending branch enters into a simple reflex arc
with the motor neuron, while the ascending branch
conveys information regarding current muscle
length to higher centers in the CNS via ascending
nerve fiber tracts in the spinal cord and brain
stem. These ascending pathways are discussed in
Section 4.8.
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Electromyogram (EMG)
Field potential of the active fibers of an SMU 1-
triphasic form 2- duration 3-15 msec 3-
discharge rate varies from 6 to 30 per second 4-
Amplitude range from 20 to 2000 ?V Surface
electrode record field potential of surface
muscles and over a wide area. Monopolar and
bipolar insertion-type needle electrode can be
used to record SMU field potentials at different
locations. The shape of SMU potential is
considerably modified by disease such as partial
denervation.
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Figure 4.11 Motor unit action potentials from
normal dorsal interosseus muscle during
progressively more powerful contractions. In the
interference pattern (c ), individual units can
no longer be clearly distinguished. (d)
Interference pattern during very strong muscular
contraction. Time scale is 10 ms per dot.
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Electroretinogram (ERG)
ERG is a recording of the temporal sequence of
changes in potential in the retina when
stimulated with a brief flash of light.
Aqueous humor
Glaucoma High pressure
A transparent contact lens contains one electrode
and the reference electrode can be placed on the
right temple.
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Electroretinogram (ERG)
Ag/AgCl electrode impeded in a special contact
lens.
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Source of Retinal Potential
There are more photoreceptors than ganglion cells
so there is a convergence pattern. Many
photoreceptors terminate into one bipolar cell
and many bipolar cells terminate into one
ganglion cell. The convergence rate is greater
at peripheral parts of the retina than at the
fovea. Rod (10 million) is for vision in dim
light and cone (3 million) is for color vision in
brighter light.
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Electroretinogram (ERG)
The a-wave, sometimes called the "late receptor
potential," reflects the general physiological
health of the photoreceptors in the outer retina.
In contrast, the b-wave reflects the health of
the inner layers of the retina, including the ON
bipolar cells and the Muller cells (Miller and
Dowling, 1970). Two other waveforms that are
sometimes recorded in the clinic are the c-wave
originating in the pigment epithelium (Marmor and
Hock, 1982) and the d-wave indicating activity of
the OFF bipolar cells (see Figure 3).
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http//webvision.med.utah.edu/ClinicalERG.html
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Electro-Oculogram (EOG)
EOG is the recording of the corneal-retinal
potential to determine the eye movement. By
placing two electrodes to the left and the right
of the eye or above and below the eye one can
measure the potential between the two electrode
to determine the horizontal or vertical movement
of the eye. The potential is zero when the gaze
is straight ahead. Applications 1- Sleep and
dream research, 2- Evaluating reading ability
and visual fatigue.
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Bionic Eyes
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Electrocardiogram (ECG)
Blood (poor with oxygen) flows from the body to
the right atrium and then to the right ventricle.
The right ventricle pump the blood to the
lung. Blood (rich with oxygen) flows from the
lung into the left atrium and then to the left
ventricle. The left ventricle pump the blood to
the rest of the body. Diastole is the resting
or filling phase (atria chamber) of the heart
cycle. Systole is the contractile or pumping
phase (ventricle chamber) of the heart
cycle. The electrical events is intrinsic to the
heart itself. See website below for the animation
of the heart. http//www.bostonscientific.com/temp
latedata/imports/HTML/CRM/heart/index.html
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Electrocardiogram (ECG)
Distribution of specialized conductive tissues in
the atria and ventricles, showing the
impulse-forming and conduction system of the
heart. The rhythmic cardiac impulse originates in
pacemaking cells in the sinoatrial (SA) node,
located at the junction of the superior vena cava
and the right atrium. Note the three specialized
pathways (anterior, middle, and posterior
internodal tracts) between the SA and
atrioventricular (AV) nodes.
Bachmann's bundle (interatrial tract) comes off
the anterior internodal tract leading to the left
atrium. The impulse passes from the SA node in an
organized manner through specialized conducting
tracts in the atria to activate first the right
and then the left atrium. Passage of the impulse
is delayed at the AV node before it continues
into the bundle of His, the right bundle branch,
the common left bundle branch, the anterior and
posterior divisions of the left bundle branch,
and the Purkinje network. The right bundle branch
runs along the right side of the interventricular
septum to the apex of the right ventricle before
it gives off significant branches. The left
common bundle crosses to the left side of the
septum and splits into the anterior division
(which is thin and long and goes under the aortic
valve in the outflow tract to the anterolateral
papillary muscle) and the posterior division
(which is wide and short and goes to the
posterior papillary muscle lying in the inflow
tract).
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SA node activates first the right and then the
left atrium. AV node delays a signal coming
from the SA node before it distribute it to the
Bundle of His. Bundle of His and Purkinie fibers
activate the right and left ventricles A typical
QRS amplitude is 1-3 mV
The P-wave shows the heart's upper chambers
(atria) contracting (depol.) The QRS complex
shows the heart's lower chambers (ventricles)
contracting The T-wave shows the heart's lower
chambers (ventricles) relaxing (repol.) The
U-wave believed to be due repolarization of
ventricular papillary muscles. P-R interval is
caused by delay in the AV node S-T segment is
related to the average duration of the plateau
regions of the individual ventricular cells.
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Steps of action potential of the ventricular
cell -Prior to excitation the resting potential
is -90 mV -Rapid Depolarization at a rate 150
V/s -Initial rapid repolarization that leads to a
fixed depolarization level for 200 t0 300
msec -Final repolarization phase that restore
membrane potential to the resting level for the
remainder of the cardiac cycle
Myofibrils
Centroid Nuclei
The cellular architecture of myocardial fibers.
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Isochronous lines of ventricular activation of
the human heart Note the nearly closed
activation surface at 30 ms into the QRS complex.
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Figure 4.16 The electrocardiography problem
Points A and B are arbitrary observation points
on the torso, RAB is the resistance between them,
and RT1 , RT2 are lumped thoracic medium
resistances. The bipolar ECG scalar lead voltage
is ?A - ?B, where these voltages are both
measured with respect to an indifferent reference
potential.
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Heart Block (dysfunctional His Bundle)
Figure 4.17 Atrioventricular block (a) Complete
heart block. Cells in the AV node are dead and
activity cannot pass from atria to ventricles.
Atria and ventricles beat independently,
ventricles being driven by an ectopic
(other-than-normal) pacemaker. (B) AV block
wherein the node is diseased (examples include
rheumatic heart disease and viral infections of
the heart). Although each wave from the atria
reaches the ventricles, the AV nodal delay is
greatly increased. This is first-degree heart
block.
60 to 70 bps
30 to 45 bps
- When one branch of the bundle of His is
interrupted, then the QRS complexes are prolonged
while the heart rate is normal.
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Arrhythmias
A portion of the myocardium sometimes becomes
irritable and discharge independently.
Figure 4.18 Normal ECG followed by an ectopic
beat An irritable focus, or ectopic pacemaker,
within the ventricle or specialized conduction
system may discharge, producing an extra beat, or
extrasystole, that interrupts the normal rhythm.
This extrasystole is also referred to as a
premature ventricular contraction (PVC).
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Figure 4.19 (a) Paroxysmal tachycardia. An
ectopic focus may repetitively discharge at a
rapid regular rate for minutes, hours, or even
days. (B) Atrial flutter. The atria begin a very
rapid, perfectly regular "flapping" movement,
beating at rates of 200 to 300 beats/min.
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Figure 4.20 (a) Atrial fibrillation. The atria
stop their regular beat and begin a feeble,
uncoordinated twitching. Concomitantly,
low-amplitude, irregular waves appear in the ECG,
as shown. This type of recording can be clearly
distinguished from the very regular ECG waveform
containing atrial flutter. (b) Ventricular
fibrillation. Mechanically the ventricles twitch
in a feeble, uncoordinated fashion with no blood
being pumped from the heart. The ECG is likewise
very uncoordinated, as shown
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Alteration of Potential Waveforms in Ischemia
Figure 4.21 (a) Action potentials recorded from
normal (solid lines) and ischemic (dashed lines)
myocardium in a dog. Control is before coronary
occlusion. (b) During the control period prior to
coronary occlusion, there is no ECG S-T segment
shift after ischemia, there is such a shift.
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Electroencephalogram (EEG)

• EEG is a superposition of the volume-conductor
  fields produced by a variety of active neuronal
  current generators. The three type of electrodes
  to make the measurements are scalp, cortical, and
  depth.
• Topics in this section
• Gross anatomy and function of the brain
• Ultrastructure of the cerebral cortex
• The potential fields of single neuron
• Typical clinical EEG waveform
• Abnormal EEG waveform

• The three main parts of the brain
• Cerebrum
• Conscious functions
• Brainstem
• primitive functions such as controlling heart
  beat
• Integration center for motor reflexes
• Thalamus is integration center for sensory system
• Cerebellum (balance and voluntary muscle movement)

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Anatomical relationship of brainstem structures
(medulla oblongata, pons, midbrain, and
diencephalons) to the cerebrum and cerebellum.
General anatomic directions of orientation in the
nervous system are superimposed on the diagram.
Here the terms rostral (toward heard), caudal
(toward tail), dorsal (back), and ventral (front)
are associated with the brainstem remaining
terms are associated with the cerebrum. The terms
medial and lateral imply nearness and remoteness
respectively, to or from the central midline axis
of the brain. (b) A simplified diagram of the CNS
showing a typical general sense pathway from the
periphery (neuron 1) to the brain (neuron 3).
Note that the axon of the secondary neuron (2) in
the pathway decussates (crosses) to the opposite
side of the cord.
Superior
Diencephalon
Cerebrum
Posterior
Anterior
Midbrain
Dorsal
Pons
Ventral
Cerebellum
Medulla oblongata
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The cerebrum, showing the four lobes (frontal,
parietal, temporal, and occipital), the lateral
and longitudinal fissures, and the central
sulcus.
The cortex receives sensory information from
skin, eyes, ears, and other receptors. This
information is compared with previous experience
and produces movements in response to these
stimuli. SER somatosensory evoked response AER
auditory evoked response VER visual evoked
response
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The outer layer (1.5 4.0 mm) of the cerebrum is
called cerebral cortex and consist of a dense
collection of nerve cells that appear gray in
color (gray matter). The deeper layer consists
of axons (or white matter) and collection of cell
body.
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Neuron Cell in the Cortex

• Two type of cells in the cortex
• Pyramidal cell
• Nonpyramidal cell
• - small cell body
• - Dendrites spring in all direction
• - Axons most of the times dont
• leave the cortex

Electrogenesis of cortical field potentials for a
net excitatory input to the apical dendritic tree
of a typical pyramidal cell. For the case of a
net inhibitory input, polarity is reversed and
the apical region becomes a source (). Current
flow to and from active fluctuating synaptic
knobs on the dendrites produces wave-like
activity.
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Bioelectric Potential From the Brain
Conducted action potentials in axons contribute
little to surface cortical records, because they
usually occur asynchronously in time and at
different spatial directions. Pyramid cells of
the cerebral cortex are oriented vertically, with
their long apical dendrites running parallel to
one another. So, the surface records obtained
signal principally the net effect of local
postsynaptic potentials of cortical
cells. Nonpyramidal cells in the neocortex are
unlikely to contribute substantially to surface
records because their dendritic trees are
radially arranged around their cells, so the
current sum to zero when viewed by electrode at a
distance. When the sum of dendritic activity is
negative relative to the cell, the cell is
depolarized and quite excitable. When it is
positive, the cell is hyperpolarized and less
excitable.
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Bioelectric Potential From the Brain

• Wave group of the normal cortex
• -Alpha wave
• - 8 to 13 Hz, 20-200 ?V,
• - Recorded mainly at the occipital region
• disappear when subject is sleep, change when
  subject change focus, see Fig. 4.27b
• -Beta wave (I and II)
• - 14 to 30Hz,
• during mental activity f50Hz, beta I disappear
  during brain activity while beta II intensified.
• Recorded mainly at the parietal and frontal
  regions
• -Theta wave
• 4 to 7 Hz, appear during emotional stress such
  as disappointment and frustration
• Recorded at the parietal and temporal regions

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Bioelectric Potential From the Brain

• -Delta wave
• Below 3.5 Hz, occur in deep sleep, occur
  independent of activity
• Occur solely within the cortex, independent of
  activities in lower regions of the brain.
• Synchronization is the underline process that
  bring a group of neurons into unified action.
  Synaptic interconnection and extracellular field
  interaction cause Synchronization.
• - Although various regions of the cortex capable
  of exhibiting rhythmic activity they require
  trigger inputs to excite rhythmicity. The
  reticular activation system (RAS) provide this
  pacemaker function.

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EEG Waves
Fig 4.27 (a) Different types of normal EEG waves.
(b) Replacement of alpha rhythm by an
asynchronous discharge when patient opens eyes.
(c) Representative abnormal EEG waveforms in
different types of epilepsy.
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International Federation 10-20 System
Type of electrode connections 1- Between each
member of a pair (bipolar) 2- Between one
monopolar lead and a distant reference 3-
Between one monopolar lead and the average of all.
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EEG Waves During Sleep
The electroencephalographic changes that occur as
a human subject goes to sleep The calibration
marks on the right represent 50 mV.
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The Abnormal EEG
EEG is used to diagnose different type of
epilepsy and in the location of the focus in the
brain causing the epilepsy. Causes of epilepsy
could be intrinsic hyperexcitability of the
neurons that make up the reticular activation
system (RAS) or by abnormality of the local
neural pathways of this system.
Two type of epilepsy 1- Generalized epilepsy
a- Grand mal b- petit mal (myoclonic
form and absence form) 2- Partial epilepsy
a- Jacksonian epilepsy b- Psychomotor
seizure (amnesia, abnormal rage, sudden anxiety
or fear, incoherent speech)